TXNIP/VDUP1 attenuates steatohepatitis via autophagy and fatty acid oxidation

Park, Hee-Seon; Song, Ji‐Won; Park, Jinho; Lim, Byung-Kwan; Moon, Og-Sung; Son, Hyeon-Taek; Lee, Jae-Hyuk; Gao, Bin; Won, Young‐Suk; Kwon, Hyojung

doi:10.1080/15548627.2020.1834711

Cited by 114 publications

(89 citation statements)

References 52 publications

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“…Targeting TXNIP may be a potential therapeutic approach for nonalcoholic steatohepatitis. 44 The reported anti-inflammatory and antifibrosis functions of TXNIP are consistent with our finding that TXNIP inhibits LPSinduced kidney injury.…”

Section: Discussionsupporting

confidence: 90%

The lncRNA CASC9 alleviates lipopolysaccharide-induced acute kidney injury by regulating the miR-424-5p/TXNIP pathway

Fan

Zhu

et al. 2021

J Int Med Res

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Objective This study aimed to clarify the mechanism by which the long non-coding RNA cancer susceptibility candidate 9 (CASC9) alleviates sepsis-related acute kidney injury (S-AKI). Methods A lipopolysaccharide (LPS)-induced AKI model was established to simulate S-AKI. HK-2 human renal tubular epithelial cells were treated with LPS to establish an in vitro model, and mice were intraperitoneally injected with LPS to generate an in vivo model. Subsequently, the mRNA expression of inflammatory and antioxidant factors was validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Reactive oxygen species (ROS) production was assessed using an assay kit. Apoptosis was detected by western blotting and fluorescence-activated cell sorting. Results CASC9 was significantly downregulated in the LPS-induced AKI model. CASC9 attenuated cell inflammation and apoptosis and enhanced the antioxidant capacity of cells. Regarding the mechanism, miR-424-5p was identified as the downstream target of CASC9, and the interaction between CASC9 and miR-424-5p promoted thioredoxin-interacting protein (TXNIP) expression. Conclusions CASC9 alleviates LPS-induced AKI in vivo and in vitro, and CASC9 directly targets miR-424-5p and further promotes the expression of TXNIP. We have provided a possible reference strategy for the treatment of S-AKI.

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Section: Discussionsupporting

confidence: 90%

The lncRNA CASC9 alleviates lipopolysaccharide-induced acute kidney injury by regulating the miR-424-5p/TXNIP pathway

Fan

Zhu

et al. 2021

J Int Med Res

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“…Dysregulated autophagy can occur for multiple reasons but current scientific literature highlighted a common link in both Mets and neurological or neurodegenerative disorders. In fact, dysfunctional lysososomal acidification may be involved, leading to consequent failure of the fusion between autophagosomes and lysosomes (Yamamoto et al, 2017;Park et al, 2020;Yamamoto et al, 2020). Although this hypothesis is very fascinating, further studies are needed to confirm this link.…”

Section: Resultsmentioning

confidence: 99%

“…A further example of the effects of autophagy is confirmed by important results showing how systemic autophagic insufficiency is able to cause deterioration of adaptation to metabolic stress and facilitate progression from obesity to diabetes (Lim et al, 2014). Recently it has been shown that Mets is characterized by a dysfunctional mitophagy (Wu H. et al, 2019) and present alterations which manifest as inadequate acidification in lysosomes (Yamamoto et al, 2017;Park et al, 2020;Yamamoto et al, 2020).…”

Section: Autophagy and Metabolic Syndromementioning

confidence: 91%

From Metabolic Syndrome to Neurological Diseases: Role of Autophagy

Maiuolo

Gliozzi

Musolino

et al. 2021

Front. Cell Dev. Biol.

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Metabolic syndrome is not a single pathology, but a constellation of cardiovascular disease risk factors including: central and abdominal obesity, systemic hypertension, insulin resistance (or type 2 diabetes mellitus), and atherogenic dyslipidemia. The global incidence of Metabolic syndrome is estimated to be about one quarter of the world population; for this reason, it would be desirable to better understand the underlying mechanisms involved in order to develop treatments that can reduce or eliminate the damage caused. The effects of Metabolic syndrome are multiple and wide ranging; some of which have an impact on the central nervous system and cause neurological and neurodegenerative diseases. Autophagy is a catabolic intracellular process, essential for the recycling of cytoplasmic materials and for the degradation of damaged cellular organelle. Therefore, autophagy is primarily a cytoprotective mechanism; even if excessive cellular degradation can be detrimental. To date, it is known that systemic autophagic insufficiency is able to cause metabolic balance deterioration and facilitate the onset of metabolic syndrome. This review aims to highlight the current state of knowledge regarding the connection between metabolic syndrome and the onset of several neurological diseases related to it. Furthermore, since autophagy has been found to be of particular importance in metabolic disorders, the probable involvement of this degradative process is assumed to be responsible for the attenuation of neurological disorders resulting from metabolic syndrome.

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“…Indeed, acute inhibition of mTOR and activation of autophagy with rapamycin in mice reduced liver injury and inflammation similarly to our study 39 . Moreover, thioredoxin interacting protein (TXNIP/VDUP1) mediates the activation of AMPK, inhibition of mTOR, and nuclear translocation of TFEB which ultimately resulted MCD diet-induced steatosis, inflammation, and fibrosis 40 .…”

Section: Discussionmentioning

confidence: 99%

Loss of hepatic Flcn protects against fibrosis and inflammation by activating autophagy pathways

Paquette

Yan

Ramírez-Reyes

et al. 2021

Sci Rep

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Non-alcoholic fatty liver disease (NAFLD) is the most frequent liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH), which is characterized by triglyceride accumulation, inflammation, and fibrosis. No pharmacological agents are currently approved to treat these conditions, but it is clear now that modulation of lipid synthesis and autophagy are key biological mechanisms that could help reduce or prevent these liver diseases. The folliculin (FLCN) protein has been recently identified as a central regulatory node governing whole body energy homeostasis, and we hypothesized that FLCN regulates highly metabolic tissues like the liver. We thus generated a liver specific Flcn knockout mouse model to study its role in liver disease progression. Using the methionine- and choline-deficient diet to mimic liver fibrosis, we demonstrate that loss of Flcn reduced triglyceride accumulation, fibrosis, and inflammation in mice. In this aggressive liver disease setting, loss of Flcn led to activation of transcription factors TFEB and TFE3 to promote autophagy, promoting the degradation of intracellular lipid stores, ultimately resulting in reduced hepatocellular damage and inflammation. Hence, the activity of FLCN could be a promising target for small molecule drugs to treat liver fibrosis by specifically activating autophagy. Collectively, these results show an unexpected role for Flcn in fatty liver disease progression and highlight new potential treatment strategies.

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TXNIP/VDUP1 attenuates steatohepatitis via autophagy and fatty acid oxidation

Cited by 114 publications

References 52 publications

The lncRNA CASC9 alleviates lipopolysaccharide-induced acute kidney injury by regulating the miR-424-5p/TXNIP pathway

The lncRNA CASC9 alleviates lipopolysaccharide-induced acute kidney injury by regulating the miR-424-5p/TXNIP pathway

From Metabolic Syndrome to Neurological Diseases: Role of Autophagy

Loss of hepatic Flcn protects against fibrosis and inflammation by activating autophagy pathways

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